截断剪接体 "绳索蛋白 "Prp45会导致依赖于Htz1的表型。

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-05-06 DOI:10.1080/15476286.2024.2348896
Kateřina Abrhámová, Martina Groušlová, Anna Valentová, Xinxin Hao, Beidong Liu, Martin Převorovský, Ondřej Gahura, František Půta, Per Sunnerhagen, Petr Folk
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引用次数: 0

摘要

剪接体的组装是剪接调控的一个重要方面,但人们对它的了解并不全面。Prp45 是一种酵母剪接因子,它在剪接体中以扩展折叠的形式运行,可能对剪接体各组分的结合非常重要。我们利用合成基因阵列技术对PRP45截短等位基因(prp45(1-169))的基因相互作用网络进行了全基因组分析,发现染色质重塑者和修饰者是一个富集类别。与相关研究一致的是,H2A.Z编码的HTZ1以及SWR1、INO80和SAGA复合物的成分是主要的相互作用者,其中htz1带来的生长缺陷最强。由于 Prp45 的截断不成比例地影响了含内含子基因的低拷贝数转录本,我们制备了携带 SRB2、VPS75 或 HRB1 的无内含子版本的菌株,它们是受影响最严重的具有转录相关功能的基因。SRB2 的内含子被去除,但其他基因的内含子未被去除,这在一定程度上修复了基因筛选中发现的一些生长表型,但并非全部。即使在删除了SRB2内含子(srb2Δi)的细胞中,也能检测到prp45(1-169)和htz1Δ的相互作用。截短程度较低的变体prp45(1-330)在16°C时与htz1Δ有合成生长缺陷,这种缺陷在srb2Δi背景下也持续存在。此外,htz1Δ还增强了prp45(1-330)依赖的前核糖核酸(pre-mRNA)的过度积累,这两种前核糖核酸分别是高效和低效接合子(基因 ECM33 和 COF1)。我们的结论是,虽然低表达内含子基因的表达缺陷促成了prp45(1-169)的基因相互作用组,但prp45和htz1等位基因之间的基因相互作用表明,prp45(1-169)中延迟的剪接体组装对染色质环境非常敏感。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Truncating the spliceosomal 'rope protein' Prp45 results in Htz1 dependent phenotypes.

Spliceosome assembly contributes an important but incompletely understood aspect of splicing regulation. Prp45 is a yeast splicing factor which runs as an extended fold through the spliceosome, and which may be important for bringing its components together. We performed a whole genome analysis of the genetic interaction network of the truncated allele of PRP45 (prp45(1-169)) using synthetic genetic array technology and found chromatin remodellers and modifiers as an enriched category. In agreement with related studies, H2A.Z-encoding HTZ1, and the components of SWR1, INO80, and SAGA complexes represented prominent interactors, with htz1 conferring the strongest growth defect. Because the truncation of Prp45 disproportionately affected low copy number transcripts of intron-containing genes, we prepared strains carrying intronless versions of SRB2, VPS75, or HRB1, the most affected cases with transcription-related function. Intron removal from SRB2, but not from the other genes, partly repaired some but not all the growth phenotypes identified in the genetic screen. The interaction of prp45(1-169) and htz1Δ was detectable even in cells with SRB2 intron deleted (srb2Δi). The less truncated variant, prp45(1-330), had a synthetic growth defect with htz1Δ at 16°C, which also persisted in the srb2Δi background. Moreover, htz1Δ enhanced prp45(1-330) dependent pre-mRNA hyper-accumulation of both high and low efficiency splicers, genes ECM33 and COF1, respectively. We conclude that while the expression defects of low expression intron-containing genes contribute to the genetic interactome of prp45(1-169), the genetic interactions between prp45 and htz1 alleles demonstrate the sensitivity of spliceosome assembly, delayed in prp45(1-169), to the chromatin environment.

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来源期刊
RNA Biology
RNA Biology 生物-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
82
审稿时长
1 months
期刊介绍: RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research. RNA Biology brings together a multidisciplinary community of scientists working in the areas of: Transcription and splicing Post-transcriptional regulation of gene expression Non-coding RNAs RNA localization Translation and catalysis by RNA Structural biology Bioinformatics RNA in disease and therapy
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